Hyperbaric resuscitation system and method

ABSTRACT

A hyperbaric resuscitation system (10) includes a hyperbaric chamber (20) having a volume sufficient to enclose a human patient (1) and at least two operating personnel (60). The system (10) also includes a device for pressurizing the hyperbaric chamber (20) to at least 1.5 atmospheres with air. The concentration of oxygen in high pressure, oxygen-rich gas to be breathed by the patient (1) provided by an independent system (41) at chamber pressure is automatically regulated by a regulating system (33) which receives information about the amount of oxygen in cerebral tissue of the patient (1) from a spectrophotometer (51, 52). Although devices for measuring the exact amount of oxygen in cerebral tissue do not yet exist, the presently available devices can show trends in the amount of oxygen in the tissue. Since the physician working on a patient in a hyperbaric resuscitation system is more concerned about trending than exact values, the present system can still be of great benefit in resuscitating patients.

CROSS-REFERENCE TO RELATED APPLICATIONS

Incorporated herein by reference are the following patent applications:co-pending U.S. patent application Ser. No. 09/108,464, filed 1 Jul.1998, which is a continuation-in-part of U.S. patent application Ser.No. 08/812,368, filed 5 Mar. 1997, which is a continuation-in-part ofU.S. patent application Ser. No. 08/348,555, filed 1 Dec. 1994.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Not applicable

REFERENCE TO A “MICROFICHE APPENDIX”

Not applicable

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to hyperbaric chambers and medicaltreatment methods and systems using hyperbaric chambers. Moreparticularly, the present invention relates to a system and method forusing a hyperbaric chamber, a spectrophotometer (preferably aNIRoscope), and an automatic regulating device which receivesinformation from the spectrophotometer to increase the amount of oxygenwhich gets to the brain of a patient being resuscitated after sufferingfrom, for example, myocardial infarction or cerebral ischemia. TheNIRoscope can also be used independently in critical care to monitor aa₃redox ratio or even be broadened to other chromophores in the brain inconjunction with neurology and mental health.

2. General Background of the Invention

Shrinking health care dollars have made the medical profession acutelyaware of the enormous cost associated with successful cardiopulmonaryresuscitations. (1,2—the parenthetical reference numerals indicate theappropriate article listed in the Appendix). The major expense isrelated to post-resuscitative care in the hospital, especially the timespent in intensive care. Cost per resuscitation depends on thepercentage of survival to hospital discharge and ranges from $550,000for 0.2% survival to $110,000 for a 10% survival. From a cost analysisperspective, it would be extremely beneficial if the number of survivorscould be increased, if their post-resuscitation condition stillpermitted them to function as independently as possible, and if thepost-resuscitation time they spent in the intensive care unit wasmarkedly reduced. For example, it has been shown that by raising theresuscitation success ratio from the present 12% to 20%, there could bea cost savings of approximately $40,000 per patient. (2) According toVirtis (1), of the 3,308,000 patients hospitalized annually, about 1%(330,800) experienced cardiac arrest and were administered CPR. If thecurrent success rate of 12.8% (3) could be raised to 20%, a nationalhealth care cost savings of $1.32 billion ($40,000×330,000) per yearcould be realized.

Although oxygen is considered to be the most important drug used inresuscitation from cardiopulmonary arrest, it is disheartening to learnthat for the past 30 years there has been little improvement inresuscitative techniques and that advances in oxygen delivery have notbeen incorporated to any meaningful extent in resuscitation.

Currently, there are at least two major limitations associated withconventional oxygen delivery: the first pertains to methods of oxygenadministration and the second pertains to the unavailability of areliable, non-invasive, direct or indirect cerebral cortical oxygenmonitor that could help assure adequate oxygenation of the brain duringCPR. Even under ideal conditions, neither masks nor endotrachealtubes—the techniques currently used for delivering oxygen duringresuscitation—deliver sufficient oxygen at sea level (1 atmosphereabsolute (atm abs)) for adequate, let alone optimum, oxygen delivery.Therefore, maximum benefit, i.e. maximum recovery of cerebral neurons(minimum residual brain damage) is not attained and, thereby, representsthe preeminent reason for the aforementioned dismal results with respectto minimizing brain damage following resuscitation from cardiopulmonaryarrest.

What is needed is a system that will provide sufficient oxygen deliveryand a sensor for non-invasively measuring in real-time the adequacy ofoxygen delivery to the cortical neurons. Hyperbaric oxygen (HBO)provides the means whereby sufficient oxygen could be delivered to thepatients. HBO increases the amount of oxygen physically dissolved in theplasma to an extent that greatly supplements that which is carried byhemoglobin in the red blood cells. More importantly, HBO provides for ahigh partial pressure of oxygen—greater than that which could beattained at sea level—which increases the rate of diffusion of theoxygen into the tissues and cells and helps assure sufficient oxygen toovercome hypoxia and maintain cellular metabolism and integrity. It isthis state of oxidative metabolism that lends itself to non-invasivemeasurement and, thereby, by inference, of adequate tissue and cellularoxygenation. Oxygen also exerts other beneficialphysiologic-pharmacologic effects which will prevent or ameliorate theonset of hypoxia-induced cerebral and cardiac pathology.

Increasing the partial pressure of oxygen inhaled during resuscitativeprocedures (pressures of oxygen that can be obtained only by hyperbaricoxygen therapy (HBOT)) is expected to be pivotal in improving thesuccess ratio of resuscitation. Such anticipation is to be expectedbecause of the documented beneficial effects of HBOT:

-   -   1. HBOT has been suggested as an indicator for identifying        potentially good resuscitative candidates. Holbach (4) reported        that if patients with cerebral ischemic damage responded well to        an initial exposure to HBOT they would continue to improve        during post-resuscitative efforts. Patients who did not respond        well to the initial HBOT exposure were less likely to recover        from ischemic damage.    -   2. Even after extended periods of cerebral ischemia,        resuscitation may be improved by HBOT (5,6)    -   3. HBOT, when used in conjunction with single photon emission        computed tomography (SPECT) (7, 8) using an appropriate        radioactive tracer has been shown to help detect the extent of        brain injury, identify if there is potentially recoverable brain        tissue, and help identify the endpoint of therapy. HBOT is        absolutely essential for recovering these neurons.

To effect successful resuscitations the oxygen dosage must be optimized.Holbach et al. reported that injured brain responds differently toincreased pressures of oxygen than does non-injured brain. Theseinvestigators demonstrated, based on regional energy utilization, that1.5 atmospheres absolute (atm abs) of oxygen is optimum for treatinginjured brain. However, Holbach was not working with resuscitationprocedures in which developing and maintaining sufficient cerebralperfusion is critical for delivering oxygen and nutrients to the neuronsand for removing end products of metabolism if a successfulresuscitation is to be effected.

In injured brain there may be damage to the cerebral circulation therebydisrupting cerebral perfusion. The major limitation of conventionalcardiopulmonary resuscitation is the failure to be able to attain andmaintain a sufficient cerebral perfusion so as to sustain cardiac andneuronal function.

HBOT represents the most efficient means of supplying sufficient oxygento tissues (neurons in the brain) thereby reversing hypoxia, sustainingneuronal metabolism, quenching free radicals, decreasing the localformation of acidosis, and stimulating angiogenesis (9). There is nodrug currently available that can do what oxygen does in enhancing thesurvival of injured neurons (10).

It is the contention of the present inventors that real-time monitoringof cellular oxidative states, an indirect but more meaningful measure oftissue oxygen tensions, would help predict whether salvageable tissuesare present. Indeed, Sheffield showed that measuring tissue oxygentensions has been used successfully as a means for predicting whichproblem wounds would respond to HBOT. Not only does this techniqueprovide predictive value, it also permits following the course oftherapy so as to gauge the efficacy of the therapeutic recoverytechniques. Thus, from a comparative perspective with respect to thebrain, measuring cerebral partial pressure of oxygen (PO₂) duringresuscitation would be an excellent gauge of successful resuscitativeefforts. Waxman et al. used the PO₂ in the muscles of the upper arm tojudge the success of resuscitation from hypovolemic shock (10). Rivers(11) measured cardiac venous PO₂ to predict the return of spontaneouscirculation while McCormick (12) measured cerebral venous PO₂ to gaugerecovery of comatose patients in intensive care. Unfortunately, no onehas yet determined what is the real-time, optimal cerebral oxygentension for tissue recovery, nor does anyone know, using currenttechnology, how to assure that there is optimal oxygen delivery duringresuscitation.

Although cerebral neurons are extremely vulnerable to hypoxia,irrespective of its etiology, there have been no reports of directmeasurements of cerebral neuronal oxidative states as a means forpredicting success of resuscitative efforts. One of the most importantreasons for the lack of such knowledge is the absence of reliable,non-invasive instrumentation for measuring cerebral neuronaloxidation-reduction states in humans.

Based on a review of the literature, the present inventors have come tobelieve that the most promising approach for the non-invasivemeasurement of cerebral oxidation-reduction states (cerebral PO₂) inhumans is one based on near infrared (NIR) spectroscopy. Measuring theratio of cerebral arterial and venous hemoglobin using NIR spectroscopyhas been accomplished while individuals were breathing air under 1 atmabs conditions. However, this technology cannot be used under HBOTconditions because the hemoglobin in both the arterial and venouscirculations may be completely saturated with oxygen. Instrumentationfor measuring the in vivo cytochrome oxidase redox ratio was usedsuccessfully in bloodless small animals. (13, 16) However, attempts toapply this technology to blood-profused large animals and humans,Matcher provided inconsistent results. It has been reported the failureto obtain consistency was due to the requirement for a higher gain todetect the cytochrome oxidase redox ratio—there is less cytochromeoxidase than hemoglobin per unit volume of brain tissue and its NIRabsorption signal is weaker. It appears that one of the basic problemsto be overcome in applying NIR spectroscopy as an aid in resuscitatingadult humans is to be able to measure the relatively weak cytochromeoxidase absorption in the presence of a pulsating hemoglobin signal thatis 10 times stronger. The effects of varying Hb absorbance, waterconcentration and tissue light scattering have led to questionableresults. (20, 21).

One desideratum for improving resuscitative efforts is a non-invasiveinstrument with sufficient sensitivity to measure the adequacy of tissueoxygen delivery in real-time at the cellular level so that attendingphysicians could optimize resuscitative efforts. Such techniques do nothave to be quantitative since it is the relative changes in redox levelsin real-time that are important.

Recent advances in spectroscopy have made it feasible for appropriateinstrumentation to be developed. For example, charged couple device(CCD) spectrophotometers have become more sensitive and can provideabsorbance spectra with integration time ranging from 10 msec to 10seconds. This alone may be adequate to monitor aa3. If not, based onmathematical models using Fourier Transform and deconvolution methods inconjunction with data obtained from a CCD in the near infrared range,the present inventors concluded that an even more sensitivespectrophotometer could be built. In fact, by applying the inventors'algorithm to synthetic (but realistic) cerebral cortex absorptionspectra, the redox ratio of cytochrome oxidase can be extracted from thespectra. Furthermore, the result of this analysis shows the realcomponent of the Fourier Transform to be linear to the cytochromeoxidase redox ratio to the fifth decimal place. Such sensitivity shouldprovide the basis for designing instrumentation that is needed formaking the necessary measurements of oxidized-reduced cytochrome oxidaseratios in real-time during cardiopulmonary resuscitation. This sametechnique may be applied to other natural chromophores in the brain suchas neuron transmitters or treatment drugs in conjunction with thediagnostics treatment of neurology and psychiatry.

Hyperbaric chambers have long been used for increasing the amount ofoxygen supplied to patients suffering from oxygen deprivation. Severalarticles and patents address this subject. However, it is important tosupply the proper amount of oxygen to a patient. Supplying too much canbe almost as harmful as supplying too little.

U.S. Pat. Nos. 3,688,770, 3,877,427, and 3,547,118 disclose hyperbaricchambers for oxygenating blood. In U.S. Pat. No. 3,547,118, a regulatorautomatically controls the relationship between the pressure of thechamber and the pressure of the oxygen supply of a patient in thechamber. U.S. Pat. No. 4,582,055 discloses a similar system.

U.S. Pat. No. 5,220,502 discloses a system for automatically measuringthe blood pressure of a patient in a hyperbaric chamber.

U.S. Pat. Nos. 4,281,645; 5,313,941; and 5,873,821 disclosespectrophotometers.

U.S. Pat. Nos. 3,984,673, 4,448,189, and 4,633,859, disclose variousapparatus for controlling the environment in hyperbaric chambers.

See also Dalago et al., SU patent document no. 395,091, December 1973;F. G. Hempel et al., “Oxidation of cerebral cytochrome aa3 by oxygenplus carbon dioxide at hyperbaric pressures,”: J. Applied Physiology:Resp.; Env., and Exercise Phys., Vol. 43, No. 5 (November 1977); and S.D. Brown et al., “In vivo binding of carbon monoxide to cytochrome coxidase in rat brain,” J. Applied Physiology, Vol. 68, No. 2 (February1990); and U.S. Pat. No. 5,251,632.

All references mentioned herein (and all references to which they refer)are hereby incorporated herein by reference.

BRIEF SUMMARY OF THE INVENTION

The present invention is a hyperbaric resuscitation method and systemincluding a hyperbaric chamber and a spectrophotometer; the systemincludes means for automatically regulating the amount of oxygen in thegas breathed by the patient by regulating the oxygen concentration andpressure of the breathed gas using information from thespectrophotometer.

The method of the present invention comprises placing a patient in ahyperbaric chamber having a volume sufficient to enclose a human patientand at least two operating personnel, pressurizing the hyperbaricchamber to greater than existing barometric pressure (preferably to atleast 1.5 atmospheres), providing oxygen-rich gas to be breathed by thepatient via a previously placed endotracheal tube, pressurizing theoxygen-rich gas to a pressure similar to that of the hyperbaric chamber,and monitoring oxygen in cerebral tissue of the patient with anon-invasive monitoring means. The method preferably also includes thestep of automatically regulating the concentration of oxygen in theoxygen-rich gas supplied to the patient via endotracheal tube inresponse to readings of the non-invasive monitoring means. The operatingpersonnel breathe chamber air which is not oxygen rich.

The present invention comprises a device, the use of which will assistin real-time evaluation of the efficacy of advanced cardiac life support(ACLS) resuscitation procedures. Specifically, the present inventioncomprises a near infrared sensor (NIRoscope) capable of non-invasivelymeasuring real-time changes in the oxidation-reduction (redox) states ofcytochrome oxidase in the cerebral cortex of patients (adults andchildren) undergoing emergency cardiopulmonary resuscitation in anhyperbaric environment. The real-time changes in redox states will beused immediately by the attending physician to assess the efficacy oftheir resuscitative efforts and to help direct changes so as to optimizethe ACLS procedures for the individual patients. The net result of theseefforts should be an enhancement of procedure efficacy thus helping toassure patient survival. In addition, successful application ofNIRoscope-assisted resuscitation procedures should also result in thepreservation of as much functional brain tissue as possible therebyyielding an increase in patients' self-reliance and a decrease in thelength of time patients are required to stay in the intensive care unitat the hospital.

As procedures are developed and stabilized, an additional improvementwould be to remotely treat the patient from outside the chamber and lockin medical personnel if complications arise.

The present invention comprises a NIRoscope capable of measuring acytochrome oxidase redox near infrared (NIR) signal with a 0.1 opticaldensity (OD) unit total range with a 0.005 OD sensitivity in a pulsating1.0 OD hemoglobin NIR signal. To test the present invention, measuredaccuracy will be evaluated by processing existing spectrum from rats, ahuman forearm and piglets, along with collected data from adolescentswine, adult humans and comparing the inventors' algorithm with thepresently used multi-component analysis algorithms available today.Results will be compared to determine which data processing method issuperior. Testing of the instrument on an existing, on-going, acuteswine model will occur at an institute under normal atmospheric andhyperbaric conditions. This testing will establish the accuracy, safetyand effectiveness of the instruments by invasive techniques. Onceaccuracy and safety have been established, the instrument will beutilized to conduct research at a major trauma center, recording theredox ratio of cytochrome oxidase in patients undergoing emergencyresuscitation. At the same time another like instrument will beincorporated into swine model resuscitation experiments on-going at thesame institution. Further testing would involve a controlled human trialof resuscitation using a NIRoscope-assisted resuscitation in anhyperbaric environment.

It is an object of the present invention to provide an integrated systemfor non-invasively measuring cerebral neuronal oxidation-reductionstates during cardiopulmonary resuscitation in an hyperbaricenvironment.

It is another object of the present invention to provide a NIRoscope anda new mathematical method that is used to enhance the instrument'ssensitivity and ability to measure, in real-time, the change in theredox state of patients undergoing resuscitation. The NIRoscope will betested in an existing acute animal resuscitation model and in a chronicextension of this model. Shortly thereafter, a NIRoscope will be used ina clinical setting to measure the changes in cerebral redox statesduring presently on-going ACLS-approved human resuscitation. It isduring this preliminary clinical test that techniques for attaching theNIRoscope to the patient will be refined and knowledge will be increasedabout the redox behavior of the cytochrome oxidase during resuscitation.Later, a clinical study comparing standard human resuscitation withhyperbaric resuscitation will be performed.

It is also an object of the present invention to provide a resuscitationmethod and system including a hyperbaric chamber and aspectrophotometer;

It is a further object of the present invention to provide aresuscitation method and system including means for automaticallyregulating the amount of oxygen in the gas breathed by the patient byregulating the oxygen concentration and pressure of the breathed gasusing information from the spectrophotometer;

It is another object of the present invention to provide a hyperbaricresuscitation system comprising a hyperbaric chamber having a volumesufficient to enclose a human patient and at least two operatingpersonnel, means for providing oxygen-rich gas through an endotrachealtube to be breathed by the patient, pressurizing means for pressurizingthe hyperbaric chamber (preferably to at least 1.5 atmospheres) and forpressurizing the oxygen-rich gas to a pressure similar to that of thehyperbaric chamber, a spectrophotometer for monitoring oxygen incerebral tissue of the patient, and regulating means for regulating theconcentration of oxygen in the oxygen-rich gas in response to readingsof the spectrophotometer.

It is another object of the present invention to provide a resuscitationmethod comprising an unmanned hyperbaric chamber sufficient to encloseone human patient, a means for providing oxygen rich gas to be breathedby the patient via an endotracheal tube with all ACLS devices placed andfixed to the patient before pressurization which can be operated fromoutside the hyperbaric chamber.

It is another object of the present invention to utilize the Niroscope'sability to non invasively monitor cerebral cortical changes inhemoglobin, water and the redox state of cytochrome oxidase, independentand without the use of HBO. The ability to observe the previousmentioned changes with the Niroscope is expected to enhance the art andscience of medicine where cellular respiration is or has been impaired.Examples include the following: in neurological rehabilitation centersas a guide for improving cerebral function after local cerebral damagedue to stroke, trauma, or exposure to toxic or anoxic encephalopathies,in the operating room as a guide for evaluating cerebral oxygenationstatus during surgery where cerebral blood flow has been compromisedi.e. bypass surgery, percutaneous transluminal coronary angioplasty, orendarterectomy; in evaluating cerebral hemodynamics and oxygenutilization in fetal and neonatal brains as a guide for detecting andmanaging hypoxic/anoxic states irrespective of etiology; in organdonation as a guide for improved management of brain-dead organ donors;and in any area of research requiring non-invasive monitoring of changesin the function of the respiratory chain (12). It is another object ofthe invention to measure the change of absorbance spectra for anynatural or synthetic chromophore that exist or is introduced in thebrain. Examples of natural chromophores would be any neurotransmitterthat has an absorbance peak in the 600–1050 nm range. An example of asynthetic drug would be any neurologic or psychiatric drug (lithium)that would be used by a neurologist or psychiatrist. The technique wouldbe to establish a baseline at some certain point and monitor the changein absorbance spectrum after a given time based on patient symptoms.Symptom and absorbance spectra could be correlated by the attendingphysician.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

For a further understanding of the nature, objects, and advantages ofthe present invention, reference should be had to the following detaileddescription, read in conjunction with the following drawings, whereinlike reference numerals denote like elements and wherein:

FIG. 1 shows theoretical absorption spectra excluding water expected tobe found during evaluation of an adult human. The axis of abscissa iswavelength (A) in nanometers, and the axis of ordinates is absorbance(Abs) in optical density. These curves were computer generated usingpublished extinction coefficients in the near infrared range (Wray1987), concentrations typically found in the brain (Cope 1988) and basedon the fact that the path lengths are equal in all cases, allowing a 1cm. value to be assumed. Each curve represents 100% oxygenatedhemoglobin (hyperbaric conditions) and various percentages of oxidizedcytochrome oxidase from 0% (bottom curve) to 100% (top curve).

FIG. 2 shows the same absorption curves of FIG. 1, with D.C. componentremoved by subtracting the average absorption value of the spectrum ateach wave length from the original spectrum.

FIGS. 3, 4, and 5 are Fourier transforms of absorbance curves. FIG. 3 is0% oxidized cytochrome oxidase, FIG. 4 is 50% oxidized cytochromeoxidase, and FIG. 5 is 100% oxidized cytochrome oxidase. The axis ofabscissa is wavenumber (N) in 1/nanometer and the axis of ordinates isthe Fourier coefficient (Fo). Notice that the only component that ischanging is the real component of the Fourier transform. It was found tobe linear to the fifth significant place (see FIG. 6).

FIG. 6 is a plot of the magnitude of the first real component of theFourier transform (axis of abscissa) versus percent oxidized cytochrome(axis of ordinate). It was found to be linear to the fifth significantfigure (i.e., in this case −0.017865) and therefore expected to be anextremely sensitive indicator of oxidized cytochrome oxidase.

FIG. 7 is a schematic diagram of the NIRoscope of the present invention.

FIG. 8 is a schematic diagram of the NIRoscope without the backgroundsignal pickup optode. The background signal is taken as reference beforethe sample signal is taken.

FIGS. 9 and 10 are side and top views, respectively, of the preferredembodiment of the apparatus of the present invention.

FIG. 11 is a top view of another embodiment of the apparatus of thepresent invention.

FIG. 12 shows the NIR light source of the present invention.

FIG. 13 is a schematic view of a single point pickup unit.

FIG. 14 is an illustrative view of a ring pickup unit (to optimize lightcollection).

FIG. 15 is schematic view of a ring pickup unit.

FIG. 16 is sectional schematic view of a ring pickup unit.

FIG. 17 is a schematic view of a Fresnel lens pickup unit with internallight input.

FIG. 18 is a schematic view of an optical arrangement of Fresnel lenspickup unit with external light input.

FIG. 19 is a schematic view of an optical arrangement of a sphericalmirror pickup unit with external light input.

FIG. 20 shows a dual wavelength interval spectrophotometer.

FIG. 21 is a diagram showing how the various features of the presentinvention are interconnected.

FIG. 22 is a diagram showing alternate features of present unit withoutreal time background measurement using the Fresnel pickup unit.

FIG. 23 is a software logic diagram (with real time backgroundmeasurement).

FIG. 24 is a software logic diagram (without real time backgroundmeasurement).

FIG. 25 shows absorption curves for hemoglobin, water and cytochromeoxidase.

PARTS LIST

The following is a list of suitable parts and materials for the variouselements of the preferred embodiment of the present invention.

-   1 patient-   2 patient's head-   3 calculated spectrum of predicted absorbance found in a human head-   4 curve of the magnitude of the Fourier transform of the absorbance    spectrum versus wave number-   5 spectrum 3 with DC component removed-   6 curve of the real component of the Fourier transform of the    absorbance spectrum versus wave number-   8 curve of the imaginary component of the Fourier transform of the    absorbance spectrum versus wave number-   9 curve of the real component of the Fourier transform (FoR) of the    absorbance spectrum versus percentage of cytochrome oxidase (% ox    aa3)-   10 hyperbaric resuscitation system (directed patient access) of the    preferred embodiment of the present invention-   20 multiplace hyperbaric chamber-   21 rolling cart in hyperbaric chamber 20-   22 quick-opening closure of hyperbaric chamber 20-   23 outer lock of hyperbaric chamber 20-   24 wall of chamber 20-   25 inside of chamber 20-   26 outside of chamber 20-   27 patient gurney-   28 wheels for quick opening closure-   31 defibrillator/cardiac monitor-   32 suction equipment-   33 regulator/ventilator-   34 code cart-   35 blood gas monitor-   36 arterial blood pressure manometer-   37 EKG monitor-   38 rectal core thermistor-   39 Thumper-Michigan CPR controls-   41 breathing gas mixer-   42 endotracheal tube connected to oxygen enriched breathing gas    mixture-   43 tunnel connecting main chamber to monoplace chamber-   51 NIR oxygen monitor (inside chamber)-   52 NIR oxygen monitor (outside chamber)-   60 emergency personnel (doctors, nurses, et al.)-   81 door-   82 door-   100 stabilized near infra-red light source-   101 light source (e.g., Oriel 66195)-   102 Lamp (e.g., 100 watt Oriel 6333)-   103 Hot mirror housing-   104 Visible light fiber optics adaptor (e.g., Oriel 77797)-   105 Hot mirror (e.g., Andover 775 FW 82-50S)-   106 Near infrared fiber optics adaptor (e.g., Oriel 77797)-   107 fiber optics light conduit-   108 Photo feedback system (e.g., Oriel 68850)-   109 Power source (e.g., DC feedback Oriel 68830)-   110 Stabilized power supply-   111 Parabolic light collector-   120 total light path-   122 visible light path-   124 NIR light path-   200 Single point pickup unit-   201 Light dam-   202 Collimating lens beam probe (light input)-   203 Collimating lens beam probe (background pickup)-   204 Collimating lens beam probe (sample pickup-cerebral cortex)-   205 Scalp-   206 Skull-   207 Dura-   208 Pia-   209 Arachnoid-   210 Cerebral cortex-   211 Multioptode ring pickup unit-   212 NIR diffuse light path (background)-   213 NIR diffuse light path (sample-cerebral cortex)-   216 fiber optic cable for light input-   218 fiber optic cable for background light-   220 fiber optic cable for sample light-   222 electric signal wire-   224 computational and control equipment-   226 optode frame with angular adjustment to light input and pickup-   228 mirror lined or polished surface-   230 Fresnel pickup unit-   231 Fiber optics bundle (e.g., Dolan Jenner XL 536T)-   232 Light dam assembly-   233 Rubber boot-   234 Fresnel lens (e.g., Edmond Scientific D43,012)-   235 Collimating lense (e.g., Donan Jenner LH 1200)-   236 Fresnel upper housing assembly-   237 Fresnel lower housing assembly-   250 spherical mirror pickup optode-   251 optode barrel-   252 encap housing-   253 mirror housing-   254 mirror cap-   255 spherical mirror (such as Edmond Scientific part no. J43-544)-   256 O-ring light seal-   300 Dual wave interval spectrophotometer-   301 Optical enclosed chopper (e.g., Oriel 75155)-   302 Bifurcated fiber optics bundle (e.g., Oriel 77533)-   303 Spectrograph (e.g., Oriel 77400)-   304 Aperture-   305 CCD Spectrophotometer-   306 Optical grating (e.g., 600–1100 nm)-   307 Charge coupled device (e.g., Oriel Inter Spec IV)-   308 Amplifier-   309 A/D converter card-   310 Interface unit-   311 Personal computer-   312 Data storage unit (e.g., Syquest)-   313 Monitor-   314 Printer-   315 Clock driver timer module-   316 Computational equipment-   400 Signal extraction processing software (with real time background    removed)-   402 Real time alternating background spectra (a 6 second integration    time and a 4 second interval time)-   403 Real time alternating sample spectra (a 6 second integration    time and a 4 second interval time)-   404 Averaging sub routine-   405 Sav-Golay 2nd degree polynomial with 51 points subroutine-   406 Fourier window (wave length interval) specified (for Hb, HbO,    H₂O, and cytochrome oxidase)-   407 DC signal removed by subtracting average absorbance from actual    value-   408 Fourier transform analysis subroutine-   409 Fourier deconvolution analysis subroutine-   410 Result stored-   411 Corrections summed-   412 individual noise (cosmic) pixels corrected subroutine-   413 Difference absorption spectra sub routine-   415 average absorbance computed (result of integral/wavelength    interval)-   416 signal extracting processing hardware (without real time    removal)-   417 first (fundamental) real component of Fourier transform-   418 real time background spectra (20 each, a 6 second integration    time and a 4 second interval time)-   450 absorbance curve for oxygenated hemoglobin-   452 absorbance curve for de-oxygenated hemoglobin-   454 absorbance curve for oxidized cytochrome oxidase-   456 absorbance curve for reduced cytochrome oxidase-   458 absorbance curve for water-   460 correction applied to cytochrome oxidase signal-   469 deoxygenated hemoglobin peak at 760 nm-   500 Dual wave interval spectrophotometer-   510 hyperbaric resuscitation system (remote patient access)-   520 monoplace hyperbaric chamber-   534 external/internal IV-   539 Thumper-Michigan chest compression device-   560 emergency room personnel (doctors, nurses, et al. (ready to    provide patient with direct access))-   611 exit ring for light input-   620 hyperbaric chamber (such as a conventional hyperbaric chamber)-   630 Optional Fresnel lens pickup unit

DETAILED DESCRIPTION OF THE INVENTION

In FIGS. 9 and 10, the preferred embodiment of the hyperbaricresuscitation system of the present invention is designated by thenumeral 10.

The system is preferably composed of a hyperbaric chamber 20 withminimum dimensions of 96″ (2.44 m) in diameter with a 14′ (4.27 m)usable length, capable of being pressurized to four atm abs, and builtto pressure vessel human occupancy (PVHO) standards. Access to thechamber 20 can be through doors 81 and 82 large enough to roll equipmentand patient 1 in and out (e.g., 34″×54″–86 cm×137 cm). Access ispreferably also provided by a quick-opening closure 22 with an openingdiameter equal to the diameter of the chamber 20. The entireresuscitation cart 21 will roll in and out of the chamber. Theresuscitation cart comprises the patient gurney 27, floor space aroundthe gurney 27 for two to five emergency personnel 60, a capnometer(monitor of CO2 in exhaled gas—not shown), a defibrillator/cardiacmonitor 31 with intravascular pressure monitoring capability, suctionequipment 32, volume cycled patient regulator/ventilator 33, AmericanHeart Association approved code cart 34, a blood gas monitor 35, anarterial line blood pressure manometer 36, continuous EKG cardiacmonitor with recorder 37, rectal core thermistor 38, x-ray equipment(not shown) for anterior/posterior neck, chest, and abdomen conventionalviews by portable x-ray equipment, a pulse oximeter (not shown) and aNIRoscope 51 capable of rapidly and continuously measuring cytochromeoxidase redox ratio in the cerebral cortex of the patient 1.

If one is willing to forego the quick-opening closure 22, one could usea standard hospital hyperbaric chamber commercially available from PerryOceonographics Company.

All NIRoscope-related equipment on the resuscitation cart 21 must bechecked for suitability for operation in an hyperbaric atmosphere and,if necessary, the requisite modifications must be made. AU aboveequipment is installed on a cart capable of being moved in and out ofthe entrance doors 81/82 of hyperbaric chamber 20.

The method of the present invention comprises placing a patient 1 withendotracheal tube in place into hyperbaric chamber 20 having a volumesufficient to enclose a human patient and at least two operatingpersonnel 60, pressurizing the hyperbaric chamber 20 to greater thanexisting barometric pressure (preferably to at least 1.5 atmospheres),providing oxygen-rich gas to be breathed by the patient 1 throughendotracheal tube 42, pressurizing the oxygen-rich gas a pressuresimilar to that of the hyperbaric chamber 20, and monitoring oxygen incerebral tissue of the patient 1 with a non-invasive monitoring means(such as NIRoscope 51, 52). The method preferably also includes the stepof automatically regulating the concentration of oxygen in theoxygen-rich gas in response to readings of the non-invasive monitoringmeans. At the option of the emergency center/attending emergencyphysician, a monoplace chamber 520 can house the patient 1 and all ACLSprocedures conducted from the outside of the chamber 520 by roboticdesign (see FIG. 11). Chamber 520 is provided with a connecting tunnel43 to chamber 620 in case patient access is needed by medical personnel560. In such a case, medical personnel 560 would enter chamber 620,chamber 620 would be pressurized to the same pressure as chamber 520,then the personnel 560 would enter chamber 520 to work with patient 1.

Description of Present Niroscope Algorithm Technology—Multi-ComponentAnalysis (MCA)

Niroscopy is the application of absorption spectroscopy in the nearinfrared range for measuring the change in concentration of specificchromophores. The primary chromophores that are designated formeasurement are oxidized and reduced cytochrome oxidase and oxygenatedand deoxygenated hemoglobin.

Currently, measuring the change of the concentration of thesechromophores by niroscopy is based on the following considerations andprocedures. Given an absorption curve over a range of wave lengths inthe near infrared region (700–950 nm) and assuming Beer's law isapplicable, a set of simultaneous equations can be generated which, whensolved, will result in concrete values for the relative concentrationsof each of the chromophores. The number of equations is equal to thenumber of chromophores whose concentrations are to be determined. Forexample, in the brain, for the near infrared spectral region, there arethe four aforementioned chromophores. If any four different nearinfrared wave lengths are selected for making total absorptionmeasurements, four total absorption values will be obtained. UsingBeer's law, it is possible to solve for the concentration of each of thechromophores. The equations that are generated will contain thefollowing variables: total absorption, chromophore extinctioncoefficients, concentration of each chromophore, and path length. Totalabsorption is obtained by direct measurement. Chromophore extinctioncoefficients are determined experimentally. Total path length involves acomplex series of events which may be considered constant for the systemand therefore can be assumed to be unity. By solving these simultaneousequations by matrix operations it is possible to calculate the relativeconcentrations of each of the chromophores. The ratio of oxidized andreduced cytochrome is then calculated from the values obtained from thesolution of the equations.

The present method has certain errors inherent in its application. Theseare:

-   -   1. The method assumes Beer's law is linear. However, Beer's law        is not linear in a scattered media or in the presence of large        absorbance changes of other chromophores.    -   2. The extinction coefficients of cytochrome have been measured        in bloodless rats where cytochrome oxidase was assumed to exist        either entirely in the oxidized or completely reduced state.        Experimental evidence has shown that a condition of total        oxidation or reduction of cytochrome oxidase does not exist.        Also a slight hemoglobin contamination was present during these        measurements for which no correction was made. Therefore, the        relative concentrations of the cytochromes that were calculated        were not accurate.    -   3. The effects of water absorption overtones cannot be taken        into account by modeling with Beer's law.    -   4. Because of the limitations associated with items 1 and 2,        current niroscopic techniques do not permit consistent        measurements in adult humans. The signal obtained in adult        humans is extremely faint since it is being masked by the high        hemoglobin concentration.

The present inventors perceived a need to develop niroscopic techniquesthat would obviate these limitations. The following is the theoreticaldescription of the bases of the innovation of the present invention.

It is the contention of the present inventors that the aforementionedlimitations of the niroscopic techniques can be overcome by the use of aspecific range of near infrared waves (600–1100 nm) from which thechange of a single absorption curve is obtained and used directly orcorrected and from which the relevant data can be extracted viamodel-free mathematical operations, i.e. Fourier transform/deconvolutionanalyses (FTA/FDA). Fourier transforms are commonly used for infraredanalysis and in digital signal filtering techniques, but are not so usedin analyses of near infrared data. There is no obvious theoreticalreason why such analyses could not be performed on data obtained fromnear infrared analyses. Therefore, the present inventors decided toincorporate such analyses in theoretical models.

The data used to demonstrate our proposed Fourier transform operationsare derived from a theoretical construct. A family of spectra isgenerated using Beer's law, and a set of measured extinctioncoefficients for each of the chromophores (Nioka 1991), and assuming acertain published physiological concentration of each chromophoreobtained from Cope (1988) and Miyake (1991). After assuming hemoglobinis 100% oxygenated, each calculated spectrum for a specific cytochromeoxidase (cyt-aa₃) redox ratio (i.e. varying from reduced to oxidized insteps of 10% is plotted as optical density versus the wave length rangeof 700 to 950 nm (FIG. 1)).

The cyt-aa₃ absorbance extraction is as follows. Each spectrum in theresultant family of spectra (FIG. 1) is subjected to removal of the DCcomponent by subtraction of the average (i.e. total area under eachcurve divided by the wave length interval), resulting in the curvesshown in FIG. 3. The curves in FIG. 3 are then subjected to Fouriertransform procedures. Form the results of Fourier transforms, it isobserved that the only value that changes as a function of thecytochrome redox ratio is the real component in the fundamentalfrequency. FIG. 2 shows the amplitude of this real component of thefundamental frequency is linearly proportional to the percent oxidizedcytochrome oxidase (i.e. redox ratio) to the fifth significant figure(i.e. 0.04212 div./redox ratio of cyt-aa₃).

The theory of Fourier transforms (Brighan 1988) explains the reason forlinearity. FIG. 25 displays the absorbance for each chromophore in the700–1100 nm wave length range. Notice that the oxidized cyt-aa₃ spectrum454 completes one cycle (i.e. the fundamental frequency in the 700–950nm wave length interval). None of the other chromophores have thisfeature. Fourier transform operator separates out the contribution ofeach component harmonic. The only spectrum completing one cycle in thechosen wave length interval is oxidized cyt-aa₃. The effect is toextract the cyt-aa₃ while filtering out all other absorbance bands.Signal extraction is improved by another Fourier transform feature. Whena Fourier transform is performed on a function (i.e. absorbancespectra), one real value and one imaginary value will be determined foreach component frequency. The real value represents the symmetricalportion of the component frequency, and the imaginary represents theasymmetrical portion of the component frequency. For a wave lengthinterval of 700–950 nm, cyt-aa₃ is symmetrical (i.e. only the realcomponent is representative) which once again extracts the cyt-aa₃absorbance peak and filters out all others. This is the reason why thereal component of the fundamental frequency is significantly linearlyproportional to cyt-aa₃ redox ratio.

The extraction technique is also quite robust with respect to signal tonoise ratios (S/N). Calculations have shown, when reducing the S/Nratios from 45 to 1.39, the fundamental real component 468 does notchange appreciably (±2%). Even when considering inexpensive, noisyspectrophotometers which have a low S/N ratio, the S/N, although low,usually remains relatively constant. It will be removed with the DCportion of absorbance spectra. This implies that as long as the signalcan be extracted (i.e. not completely buried) noise will have littleeffect. Removing the DC component and the Fourier transform also reducesthe effect of noise due to scattering.

The effects of large variations in Hb and water were studied bygenerating another theoretical construct of spectra (i.e., high and lowconcentrations for Hb and water). These spectra were processed, and theresultant real component of Fourier transfer change approximately 2%.Because our goal is to have Hb or water affect the signal by 1% or less,a second Fourier transfer tool may be required.

This second tool, Fourier deconvolution analysis (FDA) has beenexplained in detail by Blass (1981). The expected NIR total absorbancespectra is a combination of the major absorbance curves shown in FIG.25. Both de-oxygenated Hb 452 and reduced cytochrome oxidase 456 havespectra resembling exponential decay, except de-oxygenated Hb has anarrow peak 469 with a half width of 30 nm, centered at approximately760 nm. The oxygenated form of hemoglobin 450 and the oxidized state ofcytochrome oxidase 454 have broad peaks, with cytochrome oxidase havinga half width of 175 nm (725–900 nm) centered at 830 nm and deoxygenatedhemoglobin having a halfwidth of 400 nm centered at 812 nm. Because bothwater and de-oxygenated Hb have distinct peaks, Fourierself-deconvolution can be applied (Blass 1981). It is a method forresolving intrinsically overlapping absorbency bands (an NIR totalabsorbance spectrum) into each component absorption curve of interest(de-oxygenated hemoglobin and water). It is, however, noise sensitive(i.e., will resolve noise if S/N ratios are large enough) and thereforrequires an expensive (noise free) CCD spectrophotometer. If a noisefree (i.e., S/N greater than 1000) spectrophotometer is used, FDA allowsmonitoring deoxygenated hemoglobin, and water separately. If there is achange in cyt-aa₃ absorbance inflicted by Hb or water overtones, acorresponding correction can be made to the cyt-aa₃ result. The abilityto monitor cerebral edema or de-hydration (changing water content) willalso be useful information and could be easily displayed separately.

A third tool called differential absorption spectroscopy may also beutilized to enhance the extraction of the cyt-aa₃ absorbancecontribution. Rather than use an arbitrary reference (water fortransparent spectroscopy or water plus microspheres for diffusespectroscopy) a reference spectra is taken in vivo either at a certaintime (admission of the patient) or tissue location (lower distance fromlight source than sample—see FIGS. 13, 14, or 15, probe 203). Usingthese spectra as reference will allow sensitivity to be increased bymeasuring change in absorbance rather than the actual value ofabsorbance.

In summary, increasing the sensitivity of measurement with differentialabsorption spectroscopy and by combining the accurate measurement of FTAwith the possible correction to the cyt-aa₃ measurement made by FDA, wecan non-invasively measure the change in the cyt-aa₃ redox ratio with amodel-free analysis using standard digital signal conditioningtechniques. This should result in improved accuracy in adolescent swineand ultimately in the adult human head.

Data Handling Requirements

The preferred equipment (see FIG. 5) comprises a near infra-red lightsource 100, an optical pickup unit 211, and dual wave intervalspectrophotometer 300, and computational equipment 316.

Near infra-red light source 100 (see FIG. 12) is preferably a 100 wattpower light source 101 in a steady or pulsating mode (frequency range0.5–2 Hz). An example of a suitable unit would be Oriel 100 watt quartzhalogen light source with DC stabilized radiometric power supply,including photofeedback system, water filter, multiple filterholder/fiber optic adaptor (Oriel model numbers 66195, 68850, 61940,62020 and 77797).

Optical pickup unit 200/211 (see FIGS. 13,14, 15, 17, 18, 19) consistsof fiber optics light conduit 23 connected to a single or ring ofcollimating beam probes 202 which inputs the light. The background lightreceivers are recessed single or ring collimated beam probes 203adjusted at the proper angle to received background light. The samplelight is again a recessed single collimated beam probe 202 either at thecenter of the rings (FIGS. 15 and 16) or in single operation adjusted atthe proper angle to receive light input (FIG. 13) (Oriel model 77545 and77645). It should be noted that if the signal separation issatisfactorily accurate, subtraction of the background signal will notbe necessary thereby eliminating the need for 16 each background pickupoptodes 203, optical chopper 301, and bifurcated fiber optics bundle302. The preferred alternate equipment schematic is shown in FIG. 8.

Dual wave interval spectrophotometer 300 consists of an optical chopper301, bifurcated bundle 302, and CCD spectrophotometer with sensitivityadequate to measure 0.005 O.D. absorbance and a dynamic range capable ofmeasuring 4 O.D. in a wave length range of 600–1150 nm. An example of asuitable unit would be ORIEL INSTA IV CCD SYSTEM 1024×128 with instaspecwedge flange, multispec spectrograph and grating assembly (Oriel modelnumbers 77118, 77439, 77400, 77415).

Computational equipment preferably comprises a computer 311 with atleast the speed and storage capability of an IBM personal computer,Pentium with math co-processor, 10 gigabyte hard disk with tape back updrive, a National Instruments A/D converter card, LabView software forcontrol, and Galatic Grams 32/Igor software for analysis. All datastorage will preferably be done on a 105 megabyte removable cartridgetype hard disk 312 (i.e. Sydos).

The present inventors have access to a pre-existing swine model foracute resuscitation under hyperbaric oxygen conditions using externalcardiac massage. Measured parameters include EKG; EEG; arterial, mixedvenous, and sagittal sinus blood gases; arterial, pulmonary arterial,pulmonary arterial wedge, mixed venous, and sagittal sinus pressures;mixed venous and sagittal sinus hemoglobin saturation by directoximetry; cardiac output; core temperature; and expired gas. Presently,the animal is maintained for two hours after resuscitation during whichtime normal pressures and blood gases are maintained.

The model will require modification to include validation by NIRoscopemeasurements against cerebral PO₂ measurements taken by inserting anoxygen sensing electrode through a burr hole drilled in the skull. Themodel should also be extended to include a 72 hour chronic model.

Outcome indicators include:

-   -   1. Documentation of time of return of spontaneous circulation;    -   2. Normalization of arterial blood gases (ABG's);    -   3. Normalization of niroscopically determined cranial tissue        PO₂;    -   4. Serial improvement in single photon emission computerized        tomography (SPECT) brain scan by Ceretec® (technetium        hexamethylpropyleneamine oxine (HMPAO)). Case work on injured        and resuscitated divers indicates that Ceretec SPECT brain        scanning elucidates perfusion/metabolism defects in the brain.        (19);    -   5. Neurological function will be assessed using Canine Deficit        Score.

To test the system and method of the present inventions, the followinghuman studies will be conducted with proper informed consent fromimmediate family or custodial person with power of attorney.

Two groups of 20 human patients arriving in cardiopulmonary arrest atemergency departments with ongoing cardiopulmonary resuscitation andACLS will be stabilized by an emergency department hyperbaric ACLS team.The patients will be randomized into two groups. Both groups will havethe advantage of having hyperbaric environment modified MichiganInstrument automatic Thumper® and conventional ACLS pharmacology andACLS algorithmic American Heart Association protocol. The subjects willbe connected to a hyperbarically adapted volume cycled ventilator (10mg/Kg for tidal volume) by endotracheal tube. Partial arterial pressureof carbon dioxide (PaCO₂) will be maintained at 40 mm Hg by the rate ofventilation. The control group will be brought to pressure of 4 fsw(1.22 msw—meters of sea water) and administered 100% O₂ by theendotracheal tube. The niroscope will record the cerebral cortex redoxratio of cytochrome aa₃. The treatment group will be initiallyadministered 100% O₂, pressurized to minimum depths 60 fsw (18.3 msw).Once at 60 fsw (18.3 msw), both breathing gas mixture and chamberpressure will be controlled by the attending emergency physician usingthe output of the NIRoscope as a guide. Both groups will have cardiacmonitoring by EKG and arterial continuous manometry by chart recorder.The patients post resuscitation, if successful, would have SPECT brainscan by Ceretec® HMPAO utilizing a dedicated Siemens triple head highresolution radionuclide camera with three-dimensional computerreconstructed brain images to determine the extent of ischemia-inducedbrain damage and the presence of potentially recoverable brain tissue.Post-resuscitation treatment will include HBOT at 1.5 ATA (atmospheresabsolute) twice a day for three days and once a day for four days.Outcome indicators will include numbers 1 through 4 used in the animalexperiment above, as well as percentage of improvement in HBOTresuscitated patients. In addition, neurological function will beevaluated by a to-be-determined method.

The development of superior mathematical separation techniques wasnecessary because although the technology for small animals and neonateshas been available, it has not successfully been applied to adults.

The NIRoscope is considered necessary for HBOT resuscitation. It wouldalso be considered an invaluable tool for routine ACLS resuscitations atone atmosphere. Niroscopy will help to optimize treatments therebylimiting the exposure of patients and attending medical personnel topressure environments greater than that which is necessary. Thus, ithelps prevent patients from being exposed unnecessarily to too highpressures of oxygen while simultaneously helping to reduce thepossibility of dysbaric incidents in the attending personnel. Anytechnology that informs physicians as to the efficacy of theirresuscitation efforts would be extremely helpful. Three differentauthors are proposing to use tissue or blood oxygen content for helpingto evaluate success of resuscitative efforts by physicians.

The NIRoscope 51 and 52 is shown in FIGS. 12 through 21 with the totalNIRoscopic system shown in FIGS. 21 and 22. The system is composed of astabilized near infrared (NIR) light source 100 (FIG. 12) which includesa stabilized power supply 110, Quartz Tungsten Halogen light element102, a parabolic light collector 111, a hot mirror 105 which eliminatesvisible and far infrared, and fiber optics light conduit 107. A bandpass (600–1100 nm) optical (special order from Oriel) filter can also beused. NIR light is transported via a fiber optics light conduit 216 andintroduced into the patient's cranium by the pickup unit 200, 211. Thepickup unit 200, 211 can be arranged in a single point mode (FIG. 13) orfor maximum NIR light delivery, a ring arrangement (FIGS. 14, 15, and16) or without background correction (FIG. 17, 18, or 19). Referringback again to FIG. 21, NIR light is delivered to the pickup unit211/230/250 by fiber optics light conduit 216 through the wall 24 of thechamber 20 to the light input optode 202, traverses through the scalp205 (see FIG. 13), skull 206, dura matter 207, pia 208, Arachnoid 209and cerebral cortex 210, and back out again in reverse order via the NIRdiffuse light path 212, 213. It has been theoretically predicted byBonner and experimentally validated by McCormick that the depth of lightpenetration into the cranium is a function of optode spacing. An optodespacing of 5 cm has been found to be necessary to reach the cerebralcortex. Background pickup optode/ring 203 is located at a distance ofapproximately 3 cm. This distance is adequate to receive photons thathave traversed the scalp and skull but not deep enough to reach thecerebral cortex. The sample pickup optode 204 is positioned to receivephotons that have traversed the scalp, skull dura matter, and pia.Subtraction of the background signal from the sample signal results inonly the signal representing the cerebral cortex. Absorptionspectroscopy requires that the initial light source spectrum besubtracted from the measured light spectrum after traversing through thetissue. The source absorbance spectrum emanating from the cerebralcortex can be highlighted by subtracting any absorbance due to theoverlying tissues (i.e., scalp, skull, etc.), from the spectrum measuredat pickup optode 204. The spectrum from the signal pickup optode 204 andthe background pickup optode 203 are routed to the dual wave intervalspectrophotometer 300 by fiber optic conduits 218, 220 (FIG. 20). Bothsignals are received by a optical chopper 301 where they are presentedto the charge-coupled device 307 in sequence via an aperture 304 andoptical grading 306. It should be noted that electronic shutters (madeby Newport model 845 HP) could replace the optical chopper of low lightlevel applications where needed. The optical grading 306 spreads thespectrum out over the CCD in such a manner that the photon spectra isconverted into an electronic spectra which is amplified by amplifier 308and converted into a digital signal by A/D converter 309 and digitallystored by digital data storage unit 312. Proper sequencing and timing isperformed by clock driver 315.

In memory digital data storage unit 312, two data streams are stored(i.e. sample and background spectra) (see FIG. 23). Data storage unit312 has available real time alternating background spectra 402 and realtime alternating sample spectra 403. All noise pixels are corrected inall spectra 412 and smoothed by Sav-Golay smoothing function (2^(nd)degree polynomial with 51 points) 405. A difference absorption spectrumis then calculated 413 using each pair of background 402 and sample 403spectrum. An example of calculated difference absorption spectrum 3 isshown in FIG. 1. Next, the dc component of the difference spectrum 3 isremoved by integrating the spectrum 3 over the wave length span 400 to1100 nm, calculating the average wavelength adjustment by dividing theresult of the integral by the wave length span interval, and thensubtracting the resultant from each wave length absorbance value in thewave length span. An example of absorbance spectrum with DC componentremoved 5 is in FIG. 2. At this point the Fourier window 406 will beestablished. The Fourier window is the wave length interval about whichthe Fourier transform will be taken. It can be a general window whichwill separate each chromophore (i.e. oxidized and reduced cytochromeoxidase, oxyhemoglobin, deoxyhemoglobin, and water) into specificharmonic components, or a window for each chromophore can beestablished. At this point a Fourier transform 408 of the spectrum iscomputed resulting in values for each chromophore. As an alternate,Fourier deconvolution analysis 409 may be used if a more accurateindices of chromophore change is resulted. The resulting indices (forchange in oxidized and reduced cytochrome oxidase, oxyhemoglobin anddeoxyhemoglobin, and water) are stored 410 in data storage unit 312.These values may be displayed directly on monitor 313 as a function oftime start of data acquisition or summed 411 and applied 460 to correctthe cytochrome oxidase indices if the absorbance peaks are found to beinterdependent.

An alternate simplified method shown in FIG. 24 is as follows. Ratherthan taking background spectra alternately with sample spectra, a singlebackground spectrum is established before any sample spectrum is taken.Immediately after setup, a series of twenty spectra 418 are taken (forexample with 6 second exposure and 4 second interval) and stored in datastorage unit 312. Individual noise pixels are corrected 412. Thesetwenty spectra are averaged 404 resulting in one average spectrum. Theaverage spectrum is used as a constant background spectrum for theabsorbance calculation of all subsequent sample spectra. All other stepsremain the same as in FIG. 23. This technique allow a less complicatedarrangement as shown in FIG. 8 verses the more complex arrangement shownin FIG. 7.

All processing is preferably done in Pentium computer 311, withGalatic-Gram 32 software.

All of this equipment is commercially available in the form of apersonal computer and a CCD spectrophotometer made by Oriel Inc.

All optical equipment used with the present invention is preferably fromOriel Inc. All control software is preferably from National Instrumentand analytical software is preferably Grams 32 from Galatic and Igor.The computer is preferably a standard Pentium.

All measurements disclosed herein are at standard temperature andpressure, at sea level on Earth, unless indicated otherwise. Allmaterials used or intended to be used in a human being arebiocompatible, unless indicated otherwise.

APPENDIX OF REFERENCES

-   1. Virtis, M. Cost/Benefit analysis of cardiopulmonary    resuscitation: a comprehensive study-Part II. Nursing Management    23(4): 50–54, 1992.-   2. Ebell, M. & Kruse, J. A proposed model for the cost of    cardiopulmonary resuscitation. Medical Care 32(6): 640–649, 1994.-   3. Safar, P. Cerebral resuscitation after cardiac arrest: research    initiatives and future directions. Ann of Emerg Med 22(2):    2324–2349.-   4. Holbach, L., et al. Differentiation between reversible and    irreversible post-stroke changes in brain tissue: its relevance for    cerebrovascular surgery. Surg Neurol, 7: 325–331, 1977.-   5. Iwatsuki, N., et al. Hyperbaric oxygen combined with nicardipine    administration accelerates neurologic recovery after cerebral    ischemia in a canine model. Critical Care Medicine, 22(5): 858–863,    1994.-   6. Van Meter, K, Gottlieb, S., & Whidden, S. Hyperbaric oxygen as an    adjunct in ACLS on Guinea pigs after 15 minutes of cardiopulmonary    arrest. Undersea Biomedical Research, 15(Suppl): 55–56, 1988.-   7. Neubauer, R. Gottlieb, S. Enhancing “idling neurons.” Lancet 335:    542, 1990.-   8. Neubauer, R., Gottlieb, S., & Miale, A. Identification of    hypometabolic areas in the brain using brain imaging and hyperbaric    oxygen. Clinical Nuclear Medicine 17: 477–481, 1992.-   9. Neubauer, R. Gottlieb, S., Pevsner, H. Hyperbaric oxygen for    treatment of closed head injury. Southern Medical Journal 84(9):    933–936, 1994.-   10. Waxman, K., Annas, C., Daughters, K., et al. A method to    determine the adequacy of resuscitation using tissue oxygen    monitoring. Journal of Trauma 36(6): 852–857.-   11. Rivers, E., Martin, G., et al. The clinical implications of    continuous central venous oxygen saturation during human CPR. Annals    of Emergency Medicine 21: 1094–1101, 1992.-   12. McCormick, P., Stewart, G., et al. Measurement of human    hypothermic cerebral oxygen metabolism by transmission spectroscopy.    Advances in experimental medicine and biology 333: 33–41, 1993.-   13. Jobsis, F., Piantadosi, G. et al. Near infrared monitoring of    cerebral oxygen sufficiency. Neuro Resea 10: 7–17, 1988.-   14. Brazy, J. & Lewis, D. Changes in cerebral blood volume and    cytochrome aa3 during hypertensive peaks in pre-term infarcts 108:    983–987, 1986.-   15. Glaister, D., Jobsis, F. A near infrared spectrophotometric    method for studying brain O₂ sufficiency in man during +G_(z)    acceleration. Aviation, Space and Environmental Medicine 59(3):    199–207, 1988.-   16. Cope, M. et al. System for long term measurement of cerebral    blood and tissue oxygenation on newborn infants by near infrared    translumination. Med and Biol Eng Comp 26: 289–294, 1988.-   17. Hoshi, Y. Et al. Oxygen dependence of redox state of copper in    cytochrome oxidase in vitro. J App Phys 74(9): 1622–1627, 1993.-   18. Wray, S., et al. Characterization of near infrared absorption    spectra of cytochrome aa3 and hemoglobin for the non-invasive    monitoring of cerebral oxygenation, Bioch and Biophy Acta 933:    918–929, 1987.-   19. Adkisson G H, Hodgson M, Smith F, Torok Z, Macleon M A, Sykes J    J W, Strack C, Pearson R R, Cerebral perfusion deficits in dysbaric    illness, The Lancet, 2, 119–121, 1989.-   20. Matcher S, Elwell C, Cooper E, Cope M, Delpy D. Performance    comparison of several published tissue near-infrared spectroscopy    algorithms. Analytical Biochemistry 1995; 227: 54–68.-   21. Miyake H., Nioda S., Zaman A., Smith D., Chance B. The detection    of cytochrome oxidase, Heme Iron, and Copper Absorption in blood    perfused and blood free brain in Normoxia and Hypoxia Analytical    Biochemistry 1991; 192: 149–155.

Incorporated herein by reference is the paper entitled “Cytochromeoxidase reduction/oxidation charge coupled monitor with large areapickup optode” and reproduced on the following pages 30–43, whichdescribes results of the invention of the present inventors applied to aswine model.

The foregoing embodiments are presented by way of example only; thescope of the present invention is to be limited only by the followingclaims.

1. A system comprising: (a) a light source; (b) a pickup optode unit fordetecting light from the light source; (c) a spectrophotometer coupledto the pickup optode unit for sensing and recording a NIR wavelengthinterval including cytochrome oxidase, water and hemoglobin data; (d) apersonal computer with a software algorithm to extract via model-freemathematical operations the cytochrome oxidase, water and hemoglobindata from the NIR wavelength interval for evaluation and display.
 2. Thesystem of claim 1, wherein the light source is a stabilized pulsedlight.
 3. A method of using the system of claim 1 to monitor the changeof any natural or manmade chromophore existing in a person's brain toassist in the diagnosis or treatment of a neurological or psychoticdisorder, comprising: using the light source to illuminate a person'scerebral tissue; using the pickup optode unit to detect light from theperson's cerebral tissue; using the spectrophotometer to sense andrecord a NIR wavelength interval including cytochrome oxidase, water andhemoglobin data; using the personal computer and the software algorithmto extract the cytochrome oxidase, water and hemoglobin data from theNIR wavelength interval for evaluation.
 4. The method of claim 3,wherein the light source is a stabilized pulsed light.
 5. The method ofclaim 3, wherein the spectrophotometer monitors relative changes inredox levels in real-time.
 6. The method of claim 3, wherein Fouriertransforms are used in analyses of near infrared data obtained from thespectrophotometer.
 7. The method of claim 3, wherein: thespectrophotometer includes: a background pickup device which receivesphotons that have traversed the patient's scalp and skull but not deepenough to reach the patient's cerebral cortex, a sample pickup devicethat is positioned to receive photons that have traversed the patient'sscalp, skull dura matter, and pia, and the background signal issubtracted from the sample signal by the algorithm to result in a signalrepresenting the patient's cerebral cortex.
 8. The method of claim 3,wherein the light source is a quartz halogen 150 watt light source. 9.The method of claim 3, wherein the NIR wavelength interval is about700–1050 nm.
 10. The method of claim 3, wherein oxygen in cerebraltissue is monitored by monitoring cytochrome oxidase in the cerebraltissue.
 11. The method of claim 3, wherein oxygen in cerebral tissue ismonitored by monitoring the redox ratio of cytochrome oxidase in thepatient's cerebral tissue.
 12. The invention of claim 1, wherein thespectrophotometer monitors relative changes in redox levels inreal-time.
 13. The invention of claim 1, wherein the software algorithmuses Fourier transforms in analyses of near infrared data obtained fromthe spectrophotometer.
 14. The invention of claim 1, wherein: thespectrophotometer includes: a background pickup device which receivesphotons that have traversed a patient's scalp and skull but not deepenough to reach the patient's cerebral cortex, a sample pickup devicethat is positioned to receive photons that have traversed the patient'sscalp, skull dura matter, and pia, and the background signal issubtracted from the sample signal by the software algorithm to result ina signal representing the patient's cerebral cortex.
 15. The system ofclaim 1, wherein the light source is a quartz halogen 150 watt lightsource.
 16. The system of claim 1, wherein the NIR wavelength intervalis about 700–1050 nm.
 17. The invention of claim 1, comprising means formonitoring oxygen in cerebral tissue by monitoring cytochrome oxidase ina patient's cerebral tissue.
 18. The invention of claim 1, comprisingmeans for monitoring oxygen in cerebral tissue by monitoring the redoxratio of cytochrome oxidase in the cerebral tissue.
 19. The system ofclaim 1, further comprising connecting fiber optics attached to thelight source.
 20. The system of claim 19, further comprising a nearinfrared band pass filter and wherein the spectrophotometer is a dualwave interval spectrophotometer.
 21. The system of claim 1, furthercomprising a near infrared band pass filter.
 22. The system of claim 1,wherein the spectrophotometer is a dual wave interval spectrophotometer.